The investigators at Xijing Hospital in Xi?an, China are proposing a Phase I, double-blind, placebo-controlled, randomized trial of Berberine in ulcerative colitis (UC) patients who are in clinical remission, on Mesalamine for maintenance therapy. Patients with UC are at increased risk for developing colitis-associated cancer (CAC), a type of colorectal cancer. In light of this increased risk, annual colonoscopic surveillance with multiple biopsies is recommended. UC patients in remission are commonly prescribed Mesalamine, which typically helps control symptoms, but has no reported effect on cancer incidence. The incidence and prevalence of UC has been rising around the world over the last 50 years, indicating its emergence as a global disease. Berberine, a plant-derived substance that is available in the U.S. as a dietary supplement, is approved by the China Food and Drug Administration (CFDA) as an over-the-counter medication and is widely used to treat gastroenteritis and diarrhea. Berberine has shown antibacterial, anti-oxidative, and anti-inflammatory activity in several clinical trials and anti-carcinogenic activity in preclinical models. While there are extensive safety data for this compound, which is commonly given by physicians to UC patients on Mesalamine in China, and there are no known drug interactions, it has not formally been tested in combination with Mesalamine. All potential study participants will be given a copy of the IRB-approved Informed Consent to review. Subjects who refuse to participate or who withdraw from the study will be treated without prejudice. Prior to study initiation, the informed consent must be reviewed and approved by NCI, DCP, the Consortium Lead Organization and the IRB at Xijing Hospital. A professional translator expert will translate the consent into Chinese. Twelve subjects will be randomly assigned to the agent arm taking Berberine 500 mg 2x/day and four subjects will be assigned to the placebo arm for a sample size of 16. A maximum of 18 subjects will be enrolled to allow for attrition of 2 patients. All 18 subjects will have a colonoscopy at baseline and at three months, each with biopsies of the normal colonic mucosa and any inflammatory foci. Confidentiality will be maintained by assigning a numerical ID to each participant. All documents will be de-identified prior to transmission. Data will be managed by the study statistician, according to standard operating procedures, which meet the guidelines of DCP Requirements for Data Management and which follow the Data Management Plan that Northwestern University has on file with the Division of Cancer Prevention, NCI. Source data verification will be performed by the Department of Clinical Research Services. Clinical data will be reported to Northwestern University via E-mail. The principal investigator (PI) at Xijing hospital will be responsible for sending this information. Northwestern University enters data electronically to Northwestern University?s NOTIS Remote Data Capture (OC-RDC) web-based application, when available. The PI will be responsible for shipping tissue sections to an identified investigator at the Pathology Core of Northwestern University for additional histologic review upon approval of the Chinese government. Samples should be shipped every 3-4 months in batches of 4-5 subjects. All samples will be shipped in compliance with the International Air Transport Association (IATA) Dangerous Goods Regulations.